Clinical and histologic changes have been produced in rat tongue mucosa which has been infected with certain strains of Candida albicans. Chronic infection results in a flattening of the normal papillary epithelial morphology, a thickened parakeratin layer, and an overall thickening of the epithelium. These changes are similar to those seen in chronic hyperplastic candidiasis ("candidal leukoplakia") in humans. The human lesions have been described as possibly being premalignant, although it is unknown whether the epithelial changes in the human lesions are due to the candidal infection itself, or if the candidal involvement is a secondary, unrelated phenomenon which is simply superimposed upon a pre-existing leukoplakic lesion. This study would propose to examine the mucosal changes which occur during chronic candidal infection of the rat tongue, and to determine if treatment of the infection by ketoconazole, an antifungal agent, will result in a return of normal epithelial structure. If the epithelial changes appear irreversible, this would lend support to the concept that C. albicans is capable of producing leukoplakic lesions, and may suggest further studies in regard to candidiasis and carcinogenesis.